A new study reveals that specific proteins called WNT7B and WNT10A drive the aggressive behavior of a subset of pancreatic ductal adenocarcinoma (PDAC), especially the hard-to-treat basal-like subtype. While most PDAC tumors lack common WNT mutations, some cancer cells produce their own WNT ligands, which activate the WNT/β-catenin pathway and push tumors into a more aggressive, treatment-resistant state.
Researchers found that not all cancer cells make WNT. “WNT-high” cells form a short-range network, supporting nearby “WNT-low” cells through direct cell-to-cell contact. This local signaling allows aggressive cells to maintain tumor growth and survival, creating a hidden hierarchy within the tumor.
The findings suggest new treatment strategies. Blocking WNT secretion with drugs like Porcupine inhibitors can shift basal-like tumors back to a classical, chemotherapy-sensitive state. WNT7B may also serve as a biomarker to identify the most aggressive cells. This discovery opens the door to therapies that could make the toughest pancreatic cancers more responsive to standard treatments.